The specific aims of this mid-career patient-oriented research award are: 1) to further establish the candidate's independent patient- oriented clinical research program in neurohumoral mechanisms of aging cardiovascular physiology, and 20 to provide the candidate the time and resources necessary to provide mentorship to trainees pursuing clinical investigation of aging cardiovascular physiology. The candidate has a record of continuously funded productive investigation in patient- oriented research dating from the beginning of this fellowship training in Geriatric Medicine in 1985 to the present. The candidate's patient- oriented research program is funded on the role of the sympathetic nervous system (SNS) and other neurohumoral systems in the regulation of blood pressure and cardiac contractility in normal human aging, and in older patients with hypertension and heart failure. The protected time afforded by this award will permit the candidate to further develop novel methods to assess the regulation of SNS activity, adrenergic receptor function and other neurohumoral mechanisms in older patients with hypertension and heart failure. The candidate has an established record of providing mentorship of pre- and post-doctoral trainees. The candidate's research program will provide the context to permit him to continue training beginning clinical investigators. The candidate's research program and commitment to mentoring will be complemented by the special research and training program strengths of the University of Michigan (UM). These programs include outstanding clinical research facilities in a well-funded General Clinical Research Center, resource provided by several major research centers (e.g. Claude Peppers Geriatrics Center, Institute of Gerontology and Geriatric Research, Education, and Clinical Center at the Ann Arbor VA), and excellent educational resources through the curricula of the UM integrated Geriatric Fellowship Program and the School of Public Health of Science Program in Clinical Research Design and Statistical Analysis. Finally, new initiatives are being developed to facilitate innovative clinical investigation and the training of clinical investigators at the UM (e.g. the Center for Clinical Investigation and the training of clinical investigators at the UM (e.g. the Center for Clinical Investigation and Therapeutics). In summary, the candidate's accomplishment in patient- oriented research, his ability and commitment to mentor clinical investigator trainees, and the research and training strengths of the UM combine to provide an ideal context to accomplish the specific aims of this proposal.